The effect of menopause on disease activity in systemic lupus erythematosus.

OBJECTIVE: To determine the effect of menopause on disease activity and course of systemic lupus erythematosus (SLE).
METHODS: Patients were identified from the University of Toronto lupus clinic database. Menopause was diagnosed on the basis of 12 months of amenorrhea. A 3 part study was carried out. Part 1 included an inception cohort of 190 women with SLE diagnosed in the premenopausal years (Group A) and an inception cohort of 55 women with SLE diagnosed in the postmenopausal years (Group B), both followed for a minimum of 3 years. Part 2 included 49 patients followed in the clinic for at least 3 years before and 3 years after their menopause (Group C). Part 3 included 193 patients followed for 6 years entirely in the premenopausal period (Group D) and 76 patients followed for 6 years entirely in the postmenopausal period (Group E). Disease activity was measured by the SLE Disease Activity Index 2000 (SLEDAI-2K) and the adjusted mean SLEDAI-2K (AMS). Damage was assessed by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index. Comparisons were made using t-tests and chi-square and McNemar tests. A multivariate linear regression model was used to establish the impact of menopausal status on change in disease related features.
RESULTS: In the first 3 years of disease, AMS was higher in Group A than Group B (6.6 +/- 3.8 vs 5.0 +/- 3.3, p = 0.003). Damage accrual was higher in Group B than in Group A both in the first year and at 3 years. For Group C, AMS and the number of flares per 3 year interval were lower in the postmenopausal period. SLICC/ACR damage index was greater during the 3 years in the postmenopausal period then in the premenopause (p = 0.006). SLEDAI-2K was higher among Group D than Group E at the start of the study (6.71 vs 4.86, p = 0.04). AMS for the 6 years was higher in the premenopausal than postmenopausal women (5.14 vs 3.54, p </= 0.0001), however, the magnitude of change in the first and second 3 year periods was not different between Group D and E. The 3 year AMS of patients in Groups C, D, and E was plotted by age and menopausal status. The slopes of AMS in the pre- and postmenopausal periods were identical, indicating that time and not menopausal status is associated with the decrease in disease activity. On the other hand, SLICC damage index showed a greater damage in postmenopausal women at any of the time points of the study. To further delineate the effect of menopausal status on changes in disease activity and damage, multiple linear regressions were performed including age at diagnosis, disease duration, and SLEDAI-2K at presentation as independent variables. No changes in AMS, number of flares, or SLICC/ACR damage index score were associated with the menopausal status.
CONCLUSION: Although premenopausal women with SLE have more disease activity than postmenopausal women with SLE, we have shown that there is a constant rate of improvement over time, be it in the premenopause, across the menopause, or postmenopause. This improvement is not due to change in menopausal status. Thus clinicians should not be anticipating the postmenopausal era in a patient's course as a period of natural disease improvement.